6-ethyl-1-(S)-3-hydroxy-2-[(phosphonomethoxy)propyl]-5-azacytosine | 1207842-57-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 6-ethyl-1-(S)-3-hydroxy-2-[(phosphonomethoxy)propyl]-5-azacytosine
• 英文别名: [(2S)-1-(4-amino-2-ethyl-6-oxo-1,3,5-triazin-1-yl)-3-hydroxypropan-2-yl]oxymethylphosphonic acid
• CAS: 1207842-57-6
• 化学式: C₉H₁₇N₄O₆P
• 分子量: 308.231
• InChiKey: BIFIKJVOYGRGEY-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  158
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2S)-2-[(diisopropoxyphosphoryl)methoxy-3-(triphenylmethoxy)propyl]-6-ethyl-5-azacytosine 在 三甲基溴硅烷 、 三乙基碳酸氢铵缓冲液 、 甲酸 、 溶剂黄146 作用下， 以 乙腈 、 甲醇 、 水 为溶剂， 反应 48.0h， 以69%的产率得到6-ethyl-1-(S)-3-hydroxy-2-[(phosphonomethoxy)propyl]-5-azacytosine
  参考文献：
  名称：

  Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position

  摘要：

  Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.044

文献信息

• Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position
  作者：Marcela Krečmerová、Milena Masojídková、Antonín Holý

  DOI：10.1016/j.bmc.2009.10.044

  日期：2010.1

  Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus). (C) 2009 Elsevier Ltd. All rights reserved.